Many tumors and other lesions superficially resemble the parent tissues from which they arise. When such tumors are treated surgically, it has been found desirable to use various devices, such as surgical microscopes and fluorescent imaging, to help a surgeon discriminate between lesions and surrounding tissues because complete removal is associated with improved patient survival, while removal of excessive normal tissue is associated with increased morbidity.
Conventional imaging systems that are widely employed in clinical settings today, including the state-of-the-art stereoscopic high-definition microscopes, are mainly sensitive to absorption-based contrast and hence are not capable of imaging subtle morphology changes in or near real-time. Conventional microscopes often rely on staining procedures that typically require days to complete, preventing use of these techniques for immediate decision-making while incisions of a patient remain open in an operating room.
It is known that, for certain diseases including some malignant and benign tumors, disease onset and progression alters tissue morphology at the cellular and subcellular levels from normal morphology. These subtle changes in morphology cause changes in light scattering and absorption that can be used as a robust contrast mechanism for early disease diagnosis and tracking.
Localized scatter imaging using single-fiber illumination or confocal optics has been shown to be effective in detecting subtle morphology changes associated with pathologically distinct tissue types and in detecting remaining malignant tissue at surgical margins during cancer surgery, mainly because of its ability to enhance contrast between normal (or benign) and malignant tissue based on the intrinsic sensitivity of scatter to underlying microscopic tissue structure. However, one of the key limitations of this approach is that its extension to imaging has required electro-optical or mechanical scanning of a scatter-sensing head over tissue, which is often time consuming, cumbersome, and hence is not suited for many clinical applications.
Illumination of tissue with structured light and extraction of absorption and diffuse scattering parameters was described by U.S. Pat. No. 8,509,879 to Durkin, and in US patent application 2010/021093 by Cuccia. In both Durkin and Cuccia, structured light is provided to tissue at at least 2 spatial frequencies and corresponding images are obtained. A voxel-based Monte-Carlo or diffusion model of light propagation having scattering and absorption parameters is typically constructed, and these parameters are extracted by fitting parameters of the model to provide a match of model-simulated light to light as measured in the images. This model-based interpretation is required because, at their choice of spatial frequencies (usually a low and high combination in the 0-0.3 mm−1 range), the images they obtain are sensitive to both absorption and scattering properties of tissue. So their first processing step involves using a light-transport model to separate the absorption contribution from scattering contribution. These models make implicit assumptions about the underlying medium (tissue), which are often inaccurate in real world applications, particularly when interpreting superficial tissue structures.
The novel high frequency structured light imaging system and methodologies disclosed here overcomes these critical limitations and offers a fast, clinically compatible approach to diagnosing tissue-types during surgical procedures.